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This study aims to analyze the amino acid sequences and structural features of flagellins from Escherichia coli (FliCE.C), Salmonella enterica serotype Typhimurium (FliCS.T), and Pseudomonas aeruginosa (FliCP.A), and to evaluate their adjuvant activities in terms of Toll-like receptor 5 (TLR5) activation, antibody production, and cytokine responses in a murine model. (2) Methods: Bioinformatics analysis was conducted to compare the amino acid sequences and structural domains (D0, D1, D2, and D3) of flagellins from the three bacterial species. PyMol atomic models were used to confirm structural differences. Toll-like receptor 5 (TLR5) activation assays were performed to measure IL-8 and TNF-\u03b1 production in vitro. The IgG antibody titers against the model antigen FaeG and cytokine responses, including IL-4 and TNF-\u03b1 secretion were evaluated in a murine model. (3) Results: Bioinformatics analysis revealed that the D0 and D1 domains are highly conserved, whereas the D2 and D3 domains exhibit significant variability across the three species. Structural analysis via PyMol confirmed these differences, particularly in the D2 and D3 domains. TLR5 activation assays showed that FliCS.T and FliCP.A induced higher levels of IL-8 and TNF-\u03b1 production compared to FliCE.C, indicating species-specific variations in TLR5 activation. In the murine model, FliCS.T as an adjuvant produced higher antibody titers against FaeG and increased IL-4 secretion in splenocytes compared to FliCE.C and FliCP.A. FliCP.A induced higher TNF-\u03b1 expression than FliCS.T and FliCE.C, suggesting FliCS.T and FliCP.A are more effective at inducing T-cell responses. (4) Conclusions: This study highlights the potential of FliCS.T and FliCP.A as potent vaccine adjuvants. The results provide insights into the structure\u2013function relationships of these flagellins and support their application in enhancing immune responses against diverse pathogens.<\/jats:p>","DOI":"10.3390\/vaccines12111212","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T08:42:13Z","timestamp":1729845733000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Differential Adjuvant Activity by Flagellins from Escherichia coli, Salmonella\u00a0enterica Serotype Typhimurium, and Pseudomonas\u00a0aeruginosa"],"prefix":"10.3390","volume":"12","author":[{"given":"Shengmei","family":"Pang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqing","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-9142","authenticated-orcid":false,"given":"Qiangde","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/14760584.2018.1457443","article-title":"Flagellin as a vaccine adjuvant","volume":"17","author":"Cui","year":"2018","journal-title":"Expert Rev. 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